ABSTRACT The primary objective of the Cell & Tissue Models Core (Core B) is supporting the CF drug discovery efforts of participating investigators by providing state-of-the-art, CF-relevant cell and tissue models. More than 20 projects described in this renewal will utilize Core B for cell and/or tissue models. These models are used in high throughput screening assays, testing of lead compounds, therapeutically relevant preclinical bioassays, and translational science investigations of CF and airway pathophysiology. The Cell & Tissues Core achieves its objective via an infrastructure for the collection of CF-relevant tissues; instrumentation and expertise for cell isolation, culture, storage and quality control; adaptation and development of novel cell culture methods; and convenient distribution of cell models and tissues to CF investigators. Highly differentiated planar cell models of respiratory tract surface epithelial cells and submucosal gland cells that replicate native ion transport, airway surface liquid formation and mucin secretion remain the major cell model provided by the Core. In addition to our long-established strength in providing these models, the core has developed expertise in three-dimensional organotypic models (organoids), rotary wall vessel bioreactor cultures and conditionally reprogrammed cells. Organoids and rotary wall vessel bioreactor cultures provide a tissue-like environment that encourages cellular differentiation. Both methods increase the number of culture units available per tissue sample potentially generating more efficient, disease-relevant models for drug discovery. Conditionally reprogrammed cells allow expansion of CF cells through serial passaging allowing increased production of CF cell models and development of more efficient assays for evaluating small molecules. Using conditional reprogramming for producing more cell models from limited numbers of cells exhibiting rare CF genotypes will aid the development of ?personalized? therapies.